4-methyl-2-oxopentanoate

Three steps

• (7Z)-octadecenoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. carnitine O-palmitoyltransferase ((7Z)-octadecenoyl-CoA)

  Catalysed by AADAT, CPT1A, CPT1C, CPT1Bmitochondrial matrix, cytosolOne of 3 routes

• acetaldehydeReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and threonine (cytosol to extracellular)
  3. L-threonine acetaldehyde-lyase (glycine-forming)

  Catalysed by AADAT, SLC7A5extracellular space, cytosol

• CHEBI:15345Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Acetoacetate:CoA ligase (AMP-forming)

  Catalysed by AADAT, AACSmitochondrial matrix, cytosolOne of 2 routes

• cholineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of chloride and leucine (cytosol to extracellular)
  3. transport of chloride and choline (cytosol to extracellular)

  Catalysed by AADAT, SLC6A14, SLC5A7extracellular space, cytosolOne of 2 routes

• acetylpyruvateReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + L-alanine = glycine + pyruvate
  3. acetylpyruvate + H2O = acetate + pyruvate + H(+)

  Catalysed by AADAT, AGXT, AGXT2, FAHD1

• all-trans-retinoic acidReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + L-alanine = glycine + pyruvate
  3. transport of pyruvate and retinoate (cytosol to extracellular)

  Catalysed by AADAT, AGXT, AGXT2, SLC16A4 and 5 moreextracellular space, cytosolOne of 2 routes

• 4a-hydroxytetrahydrobiopterinReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and tryptophan (cytosol to extracellular)
  3. L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase(5-hydroxylating)

  Catalysed by AADAT, SLC7A5, TPH1, TPH2extracellular space, cytosolOne of 3 routes

• CHEBI:15380Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. 5-aminolevulinate synthase (2-amino-3-oxoadipate)

  Catalysed by AADAT, ALAS1, CPNE7mitochondrial matrixOne of 8 routes

• CHEBI:15477Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. glycine N-acyltransferase (2-methylbutyryl-CoA)

  Catalysed by AADAT, GLYAT, GLYATL2, GLYATL1mitochondrial matrixOne of 2 routes

• 2-methylcrotonoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Production of Tiglylcarnitine

  Catalysed by AADAT, CPT1A, CPT1Bmitochondrial matrix, cytosolOne of 2 routes

• isobutyryl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. acetyl-CoA C-acyltransferase (3-oxo-4-methyl-pentanoyl-CoA)

  Catalysed by AADAT, HADHA, ACAA2, HADHBmitochondrial matrixOne of 3 routes

• 3-methylbut-2-enoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. glycine-N-acyltransferase (3-methylcrotonoylglycine)

  Catalysed by AADAT, GLYATmitochondrial matrix

• isovaleryl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. glycine N-acyltransferase (isovalerylglycine)

  Catalysed by AADAT, GLYAT, GLYATL2, GLYATL1mitochondrial matrixOne of 3 routes

• arachidonoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Arachidonate:CoA ligase (AMP-forming)

  Catalysed by AADAT, SLC27A2, ACSL4, ACSL3 and 5 moremitochondrial matrix, cytosolOne of 11 routes

• CHEBI:15519Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. propanoyl-CoA C-acyltransferase

  Catalysed by AADAT, ACAA1, SCP2, MYO5Bmitochondrial matrix, peroxisomeOne of 2 routes

• palmitoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Palmitate:CoA ligase (AMP-forming)

  Catalysed by AADAT, SLC27A2, ACSL4, ACSL3 and 5 moremitochondrial matrix, cytosolOne of 11 routes

• oleoyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Transport of octadecenoyl-CoA into Mitochondrial Matrix

  Catalysed by AADAT, CPT1A, CPT1C, CPT1Bmitochondrial matrix, cytosolOne of 11 routes

• phenylacetyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Phenylacetate:CoA ligase

  Catalysed by AADATmitochondrial matrix, cytosolOne of 3 routes

• propionyl-CoAReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Propanoate:CoA ligase (AMP-forming)

  Catalysed by AADAT, ACSS3, ACSS2, ACSS1mitochondrial matrix, cytosolOne of 44 routes

• CHEBI:15570Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of glycine and leucine (cytosol to extracellular)
  3. transport of D-alanine and glycine (cytosol to extracellular)

  Catalysed by AADAT, SLC7A5, SLC3A2, SLC7A10extracellular space, cytosolOne of 5 routes

• CHEBI:15611Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of glycine and leucine (cytosol to extracellular)
  3. S-Adenosyl-L-methionine:glycine N-methyltransferase

  Catalysed by AADAT, SLC7A5, GNMTextracellular space, cytosol

• (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterinReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and tryptophan (cytosol to extracellular)
  3. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin

  Catalysed by AADAT, SLC7A5, TPH1, TPH2extracellular space, cytosolOne of 2 routes

• CHEBI:15650Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. N-acetyl-LTE4 to leukotriene E4 conversion

  Catalysed by AADAT, ZDHHC11B, NAA10, ESCO2 and 29 moremitochondrial matrix, cytosolOne of 2 routes

• trimethylenediamineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and lysine (cytosol to extracellular)
  3. deoxyhypusine synthase (1,3-diaminopropane)

  Catalysed by AADAT, SLC7A6, DHPSextracellular space, cytosol

• CHEBI:15727Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of histidine and leucine (cytosol to extracellular)
  3. L-histidine:beta-alanine ligase (ADP-forming)

  Catalysed by AADAT, SLC7A6, CARNS1extracellular space, cytosolOne of 2 routes

• formateReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + O2 + H2O = oxalate + H2O2 + H(+)
  3. oxalate(in) + formate(out) = oxalate(out) + formate(in)

  Catalysed by AADAT, HAO1, SLC26A6inner side of the membrane, outer side of the membraneOne of 2 routes

• CHEBI:15746Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. diamine N-acetyltransferase (N1-acetylspermine)

  Catalysed by AADAT, SAT1, SAT2mitochondrial matrix, cytosolOne of 2 routes

• malonateReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + acetyl-CoA + H2O = (S)-malate + CoA + H(+)
  3. malonate(out) + (S)-malate(in) = malonate(in) + (S)-malate(out)

  Catalysed by AADAT, CLYBL, SLC25A10inner side of the membrane, outer side of the membraneOne of 2 routes

• N-carbamoyl-L-aspartic acidReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. L-leucine(out) + L-aspartate(in) = L-leucine(in) + L-aspartate(out)
  3. carbamoyl-phosphate:L-aspartate carbamoyltransferase

  Catalysed by AADAT, SLC7A13, CADinner side of the membrane, outer side of the membrane, cytosol

• alpha-D-glucosamine 6-phosphateReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of glutamine and leucine (cytosol to extracellular)
  3. L-glutamine:D-fructose-6-phosphate isomerase (deaminating)

  Catalysed by AADAT, SLC7A5, GFPT2, GFPT1extracellular space, cytosol

• homogentisateReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. L-tyrosine + glyoxylate = 3-(4-hydroxyphenyl)pyruvate + glycine
  3. 4-Hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating,decarboxylating)

  Catalysed by AADAT, HPDcytosolOne of 2 routes

• sulfateReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of chloride and leucine (cytosol to extracellular)
  3. transport of chloride and sulfate (cytosol to extracellular)

  Catalysed by AADAT, SLC6A14, SLC26A6extracellular space, cytosolOne of 11 routes

• ureaReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of arginine and leucine (cytosol to extracellular)
  3. L-Arginine amidinohydrolase

  Catalysed by AADAT, SLC3A2, SLC7A6, SLC7A7 and 1 moreextracellular space, cytosolOne of 3 routes

• 2-methyl-3-oxopropanoic acidReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + L-alanine = glycine + pyruvate
  3. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase

  Catalysed by AADAT, AGXT, AGXT2mitochondrial matrix

• CHEBI:16284Reach from here →
  1. branched chain keto acid dehydrogenase E1 (4-methyl-2-oxopentanoate)
  2. lipoamide to S-(3-methylbutanoyl)... conversion
  3. Antiport of thiamine-diphosphate and dATP

  Catalysed by BCKDHA, BCKDHB, DBT, SLC25A19mitochondrial matrix, cytosolOne of 2 routes

• 11-cis-retinolReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. Palmitoyl-CoA:retinol O-acyltransferase

  Catalysed by AADAT, DGAT1, LRAT, AWAT1 and 2 moremitochondrial matrix, cytosol

• (R)-3-aminoisobutyric acidReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of alanine and leucine (cytosol to extracellular)
  3. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase

  Catalysed by AADAT, SLC7A5, AGXT2extracellular space, cytosol, mitochondrial matrix

• (R)-carnitineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. kynurenate(out) + glutarate(in) = kynurenate(in) + glutarate(out)
  3. glutarate(in) + (R)-carnitine(out) = glutarate(out) + (R)-carnitine(in)

  Catalysed by AADAT, SLC22A6, SLC22A8inner side of the membrane, outer side of the membraneOne of 2 routes

• iodideReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and tyrosine (cytosol to extracellular)
  3. thyroid peroxidase (iodine)

  Catalysed by AADAT, SLC7A5, TPOextracellular space, cytosolOne of 3 routes

• oxaloacetateReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Acetylation of Leucine
  3. ATP citrate lyase (citrate)

  Catalysed by AADAT, ACLYmitochondrial matrix, cytosolOne of 15 routes

• nitric oxideReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of arginine and leucine (cytosol to extracellular)
  3. L-Arginine, NADPH:Oxygen Oxidoreductase (Nitric-Oxide-Forming)

  Catalysed by AADAT, SLC3A2, SLC7A6, SLC7A7 and 3 moreextracellular space, cytosolOne of 2 routes

• CHEBI:16523Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of glycine and leucine (cytosol to extracellular)
  3. transport of D-serine and glycine (cytosol to extracellular)

  Catalysed by AADAT, SLC7A5, SLC3A2, SLC7A10extracellular space, cytosolOne of 4 routes

• N(2)-acetyl-L-ornithineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and ornithine (cytosol to extracellular)
  3. N2-Acetyl-L-ornithine amidohydrolase

  Catalysed by AADAT, SLC7A6, ACY1extracellular space, cytosol

• 2-phenylacetamideReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and phenylalanine (cytosol to extracellular)
  3. L-phenylalanine:oxygen 2-oxidoreductase (decarboxylating)

  Catalysed by AADAT, SLC7A5, EPXextracellular space, cytosol

• anthranilateReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. Transport of L-Kynurenine
  3. L-kynurenine + H2O = anthranilate + L-alanine + H(+)

  Catalysed by AADAT, SLC43A1, KYNUextracellular space, cytosol

• CHEBI:16633Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of alanine and leucine (cytosol to extracellular)
  3. L-selenocysteine selenide-lyase (L-alanine-forming)

  Catalysed by AADAT, SLC7A5, SCLYextracellular space, cytosol

• Met-tRNA(Met)Reach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and methionine (cytosol to extracellular)
  3. L-Methionine:tRNAMet ligase (AMP-forming)

  Catalysed by AADAT, SLC3A2, SLC7A5, MARS1extracellular space, cytosol

• (S)-lactateReach from here →
  1. L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine
  2. glyoxylate + L-alanine = glycine + pyruvate
  3. (S)-lactate + NAD(+) = pyruvate + NADH + H(+)

  Catalysed by AADAT, AGXT, AGXT2, LDHA and 4 more

• N-[(S)-lactoyl]-L-phenylalanineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and phenylalanine (cytosol to extracellular)
  3. (S)-lactate + L-phenylalanine = N-[(S)-lactoyl]-L-phenylalanine + H2O

  Catalysed by AADAT, SLC7A5, CNDP2extracellular space, cytosol

• tryptamineReach from here →
  1. 4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O
  2. transport of leucine and tryptophan (cytosol to extracellular)
  3. L-tryptophan decarboxy-lyase

  Catalysed by AADAT, SLC7A5, DDCextracellular space, cytosol